High CD169 Monocyte/Lymphocyte Ratio Reflects Immunophenotype Disruption and Oxygen Need in COVID-19 Patients

Antonella Minutolo (1) , Vita Petrone (1) , Marialaura Fanelli (1) , Marco Iannetta (1, 2) , Martina Giudice (1) , Ines Ait Belkacem (3, 4) , Marta Zordan (1, 2) , Pietro Vitale (2) , Guido Rasi (1) , Paola Sinibaldi-Vallebona (1, 5) , Loredana Sarmati (1, 2) , Massimo Andreoni (2, 1) , Fabrice Malergue (4) , Emanuela Balestrieri (1) , Sandro Grelli (1) , Claudia Matteucci (1)

1 University of Rome "Tor Vergeta"
2 Department of Laboratory Medicine, Policlinico "Tor Vergata ", Rome, Italy
3 CIML - Centre d'Immunologie de Marseille - Luminy
4 Immunotech-Beckman Coulter
5 National Research Council (CNR), Rome, Italy

Background: Sialoadhesin (CD169) has been found to be overexpressed in the blood of COVID-19 patients and identified as a biomarker in early disease. We analyzed CD169 in the blood cells of COVID-19 patients to assess its role as a predictive marker of disease progression and clinical outcomes. Methods: The ratio of the median fluorescence intensity of CD169 between monocytes and lymphocytes (CD169 RMFI) was analyzed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HDs) and correlated with immunophenotyping, inflammatory markers, cytokine mRNA expression, pulmonary involvement, and disease progression. Results: CD169 RMFI was high in COV but not in HDs, and it correlated with CD8 T-cell senescence and exhaustion markers, as well as with B-cell maturation and differentiation in COV. CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients who were untreated at sampling, and was associated with the respiratory outcome throughout hospitalization. Finally, we also report the first evidence of the specific ability of the spike protein of SARS-CoV-2 to trigger CD169 RMFI in a dose-dependent manner in parallel with IL-6 and IL-10 gene transcription in HD PBMCs stimulated in vitro. Conclusion: CD169 is induced by the spike protein and should be considered as an early biomarker for evaluating immune dysfunction and respiratory outcomes in COVID-19 patients.

Mots clés: cytokine storm; COVID-19; CD169; inflammation; respiratory outcome; T-cell exhaustion; COVID-19 therapy

Domaines: Sciences du Vivant [q-bio]

Antonella Minutolo, Vita Petrone, Marialaura Fanelli, Marco Iannetta, Martina Giudice, et al.. High CD169 Monocyte/Lymphocyte Ratio Reflects Immunophenotype Disruption and Oxygen Need in COVID-19 Patients. Pathogens, 2021, 10 (12), pp.1639. ⟨10.3390/pathogens10121639⟩. ⟨hal-03623545⟩